Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond 6 years.

Scrapie is a transmissible spongiform encephalopathy of sheep and goats, and scrapie eradication programs in many parts of the world rely on strong genetic resistance to classical scrapie in sheep. However, the utility of putative resistance alleles in goats has been a focus of research because goats can transmit scrapie to sheep and may serve as a scrapie reservoir. Prior work showed that disease-free survival time was significantly extended in orally inoculated goats singly heterozygous for prion amino acid substitutions S146 or K222, but average durations were only around 3 years post-inoculation. The aim of this study was to investigate whether extended survival would exceed 6 years, which represents the productive lifetimes of most commercial goats. While all control homozygotes were clinically affected by an average of <2 years, none of the NS146 or QK222 goats developed clinical scrapie or had PrPSc-positive rectal biopsies. Several NS146 and QK222 goats developed other conditions unrelated to scrapie, but tissue accumulation of PrPSc was not detected in any of these animals. The NS146 heterozygotes have remained disease-free for an average of 2734days (approximately 7.5 years), the longest duration of any classical scrapie challenge experiment with any genotype to date. The QK222 heterozygotes have remained disease-free for an average of 2450days (approximately 6.7 years), the longest reported average duration for QK222 goats challenged with classical scrapie. This research is ongoing, but the current results demonstrate S146 and K222 confer strong resistance to classical scrapie in goats.

Periostin normalizes levels of cardiac markers in rats with experimental isoproterenol cardiotoxicity.

BACKGROUND: Although the molecular mechanism of cardiac healing is not fully understood, myocardial infarction is one of the most usual diagnoses in hospitalized patients in industrialized nations while periostin has been recently suggested to have a potential in tissue repairing following myocardial ischemia. OBJECTIVES: To investigate the effects of periostin on the levels of selected cardiac parameters (cardiac troponin I and T, creatine kinase and creatine kinase isoenzyme-MB), antioxidant/lipid peroxidation parameters (superoxide dismutase, catalase, and malondialdehyde), hepatic parameters (alkaline phosphatase, lactate dehydrogenase, aspartate and alanine transaminases) as well as lipids (total cholesterol, triglyceride, high, low and very­low­density lipoproteins) in a rat model of isoproterenol---induced myocardial injury. METHODS: A total of 84 male rats were grouped into saline (Group I), periostin (Group II), isoproterenol (Group III) and isoproterenol+periostin (Group IV) groups (n = 21). Isoproterenol (85 mg/kg/day) and periostin groups were both injected intraperitoneally (1 µg/kg). RESULTS: Our results revealed that periostin has a positive reducing effect on the levels of analysed parameters especially on cardiac troponins and creatine kinases on days 7 and 28 of the recovery period following the induced experimental heart damage in rats. CONCLUSION: It is concluded that periostin could have a potential to increase the rate of myocardial recovery after myocardial infarction (Tab. 5, Ref. 28).

Thiophene-Based Organic Semiconductors.

Thiophene-based π-conjugated organic small molecules and polymers are the research subject of significant current interest owing to their potential use as organic semiconductors in material chemistry. Despite simple and similar molecular structures, the hitherto reported properties of thiophene-based organic semiconductors are rather diverse. Design of high performance organic semiconducting materials requires a thorough understanding of inter- and intra-molecular interactions, solid-state packing, and the influence of both factors on the charge carrier transport. In this chapter, thiophene-based organic semiconductors, which are classified in terms of their chemical structures and their structure-property relationships, are addressed for the potential applications as organic photovoltaics (OPVs), organic field-effect transistors (OFETs) and organic light emitting diodes (OLEDs).

Triarylborane-Based Materials for OLED Applications.

Multidisciplinary research on organic fluorescent molecules has been attracting great interest owing to their potential applications in biomedical and material sciences. In recent years, electron deficient systems have been increasingly incorporated into fluorescent materials. Triarylboranes with the empty p orbital of their boron centres are electron deficient and can be used as strong electron acceptors in conjugated organic fluorescent materials. Moreover, their applications in optoelectronic devices, energy harvesting materials and anion sensing, due to their natural Lewis acidity and remarkable solid-state fluorescence properties, have also been investigated. Furthermore, fluorescent triarylborane-based materials have been commonly utilized as emitters and electron transporters in organic light emitting diode (OLED) applications. In this review, triarylborane-based small molecules and polymers will be surveyed, covering their structure-property relationships, intramolecular charge transfer properties and solid-state fluorescence quantum yields as functional emissive materials in OLEDs. Also, the importance of the boron atom in triarylborane compounds is emphasized to address the key issues of both fluorescent emitters and their host materials for the construction of high-performance OLEDs.

Electrochemical oxidation mechanism of eugenol on graphene modified carbon paste electrode and its analytical application to pharmaceutical analysis.

Electrochemical properties of eugenol were investigated on a graphene modified carbon paste electrode (CPE) by using voltammetric methods, which exhibited a well-defined irreversible peak at about 0.7V vs Ag/AgCl, NaCl (3M) in Britton-Robinson buffer at pH 2.0. Mechanism of the electrochemical reaction of eugenol was studied by performing density functional theory (DFT) computations and mass spectroscopic analysis. (CPCM:water)-wB97XD/aug-cc-PVTZ//(CPCM:water)-wB97XD/6-31G(d) level calculations predicted that the formation of product P2, possessing a para-quinoid structure, is preferred rather than the product P1, suggested in the literature, having an ortho-quinoid system. Determination of eugenol in a pharmaceutical sample was realized in the light of the electrochemical findings, and a validated voltammetric method for quantitative analysis of eugenol in a pharmaceutical formulation was proposed. The differential pulse voltammogram (DPV) peak currents were found to be linear in the concentration range of 1.0 × 10-7 to 1.7 × 10-5M. The limit of detection (LOD) and the limit of quantification (LOQ) were obtained to be 7.0 × 10-9 and 2.3 × 10-8, respectively.

Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes.

A one-pot transformation, which involves the reaction of ketones with aldehydes in the presence of metal halides to furnish tetrahydro-2H-pyran-2,4-diols in a highly diastereoselective manner, is investigated thoroughly by experiments and computations. The reaction was also successfully implemented on a flow micro reactor system.

Risk factors for malignancy in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

Mechanistic Information from Nonstationary Points.

The thermal cyclization of enyne-carbodiimides substituted at both the alkyne and carbodiimide terminus showed two curved Hammett correlations (log k/k0 against σp) that were fully reproduced by DFT (density functional theory) computational results. The latter suggest a concerted mechanism, but the transition state (TS) analysis failed to reveal any mechanistic insight about the reason for a curved Hammett correlation. Instead a preTS inspection, i.e., examination of the electronic and steric details on route between reactant and TS, furnished a detailed picture of the mechanism.

Effects of dietary boron and phytase supplementation on growth performance and mineral profile of broiler chickens fed on diets adequate or deficient in calcium and phosphorus.

1. Two experiments were designed to determine the effect of dietary boron (B) in broiler chickens. In Experiment 1, a 2 × 4 factorial arrangement of treatments was used to investigate the effect of dietary calcium (Ca) and available phosphorus (aP) (adequate or deficient) and supplemental B (0, 20, 40, and 60 mg/kg diet). In Experiment 2, B, at 20 mg/kg, and phytase (PHY) (500 FTU/kg diet) were incorporated into a basal diet deficient in Ca and aP, either alone or in combination. 2. The parameters that were measured were growth performance indices, serum biochemical activity as well as ash and mineral (i.e. Ca, P, Mg, Fe, Cu and Zn) content of tibia, breast muscle and liver. 3. Results indicated that both supplemental B and dietary Ca and aP had marginal effects on performance indices of chickens grown for 42 d. 4. There were positive correlations (linear effect) between B concentrations of serum, bone, breast muscle and liver and the amount of B consumed. 5. Serum T3 and T4 activities increased linearly with higher B supplementation. 6. Increasing supplemental B had significant implications on breast muscle and liver mineral composition. Lowering dietary Ca and aP level increased Cu content in liver and both Fe and Zn retention in breast muscle. Tibia ash content and mineral composition did not respond to dietary modifications with either Ca-aP or B. 7. The results also suggested that dietary contents of Ca and aP do not affect the response to B regarding tissue mineral profile. Dietary combination with B and PHY did not create a synergism with regard to growth performance and bioavailability of the minerals.

One-Pot Domino Aldol Reaction of Indium Enolates Affording 6-Deoxy-α-D,L-altropyranose Derivatives: Synthesis, Mechanism, and Computational Results.

The domino-aldol-aldol-hemiacetal-reaction cascade of indium and other group 13 metal enolates furnished 6-deoxy-α-D,L-altropyranose derivatives in up to 99% yield under thermodynamic control. At lower temperature and thus under kinetic control, the reaction proceeded in a much less diastereoselective manner. The changeover from kinetic to thermodynamic control operating in this multistep domino-aldol-aldol-hemiacetal protocol was used for probing the efficiency of DFT computations. Calculations at the B3LYP/6-31G(d)/LANL2DZ level provided a mechanistic picture in full agreement with the experimental outcome.

Spectral features, electric properties, NBO analysis and reactivity descriptors of 2-(2-Benzothiazolylthio)-Ethanol: Combined experimental and DFT studies.

Quantum chemical calculations of ground state energy, geometrical structure and vibrational wavenumbers, nuclear magnetic behaviors, electronic absorption spectra along with the nonlinear optical properties of 2-(2-benzothiazolylthio)-ethanol (BTZTE) were carried out using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The FT-IR and FT-Raman spectra were measured in the condensed state. The fundamental vibrational wavenumbers as well as their intensities were calculated, and a good correlation between experimental and scaled calculated wavenumbers was accomplished. The electric dipole moment, polarizability and the first hyperpolarizability values of the BTZTE were calculated at the same level of theory and basis set. The results show that the BTZTE molecule possesses nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. UV spectrum of the studied molecule was recorded in the region 200-500nm and the electronic properties were predicted by time-dependent DFT approach. The calculated transition energies are in good concurrency with the experimental data. (1)H nuclear magnetic resonance (NMR) chemical shifts of the title molecule were calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. The thermodynamic properties of the studied compound at different temperatures were calculated. Global and local reactivity descriptors were computed to predict reactivity and reactive sites on the molecule.

Evaluation of the sustainability of contrasted pig farming systems: the procedure, the evaluated systems and the evaluation tools.

Although a few studies consider the sustainability of animal farming systems along the three classical main pillars (economy, environment and society), most studies on pig farming systems address only one of these pillars. The present paper is the introduction to a series of companion papers presenting the results of a study undertaken within the EU-supported project Q-PorkChains, aiming at building a comprehensive tool for the evaluation of pig farming systems, which is robust to accommodate the large variability of systems existing in Europe. The tool is mostly based on questions to farmers and comprises a total of 37 dimensions distributed along eight themes: Animal Welfare, Animal Health, Breeding Programmes, Environmental Sustainability, Meat Safety, Market Conformity, Economy and Working Conditions. The paper describes the procedure that was used for building the tool, using it on 15 contrasted pig farming systems and analysing the results. The evaluated systems are briefly described and a short overview of the dimensions is provided. Detailed descriptions of the theme-wise tools and results, as well as the results of an integrated evaluation, are available in the companion papers.

Evaluation of the sustainability of contrasted pig farming systems: integrated evaluation.

The aim of this paper is to present an approach for an integrated evaluation of the sustainability of pig farming systems, taking into account the three classical pillars: economy, environment and society. Eight sustainability themes were considered: Animal Welfare (AW), Animal Health (AH), Breeding Programmes (BP), Environment (EN), Meat Safety (MS), Market Conformity (MC), Economy (EC) and Working Conditions (WC). A total of 37 primary indicators were identified and used for the evaluation of 15 much contrasted pig farming systems in five EU countries. The results show that the eight themes were not redundant and all contributed to the observed variation between systems. The tool was very robust for highlighting the strengths and weaknesses of the systems along the eight themes that were considered. The number of primary indicators could be reduced from 37 to 18 with limited impact on the strengths/weaknesses profile of the individual systems. Integrating the eight theme evaluations into a single sustainability score is based on hypotheses or presumptions on the relative weights that should be given to the eight themes, which are very dependent on the context and on the purpose of the users of the tool. Therefore, the present paper does not have the ambition to provide a ready-for-use tool, rather to suggest an approach for the integrated evaluation of the sustainability of pig farming systems.

The effects of magnesium sulphate on the contractile activity of uterus in an animal model of preeclampsia.

PURPOSE: This study was undertaken to evaluate the effects of magnesium sulfate (MgSO4) on the contractile activity of the uterus in a pregnant rat model of preeclampsia induced by N-nitro-arginine methyl ester (L-NAME). MATERIALS AND METHODS: Twenty-eight, 160-220 gram, three to four month old female Sprague-Dawley rats were used in this study. After conception was confirmed by vaginal smears on the first day of pregnancy, the animals were allocated into four groups according to the chemicals fed in their drinking water as control (nothing administered), L-NAME (50 mg/kg L-NAME), MgSO4 (600 mg/kg MgSO4), and MgSO4 + L-NAME group (600 mg/kg MgSO4 + 50 mg/kg L-NAME). The pregnant uterus strips were isolated on the 19th day and the contractile activity of uterus was examined by applying 0, 0.1, 0.2, 0.4, 0.8, and 2.5 mIU/ml oxytocin to each group and responses are recorded accordingly. RESULTS: There were no statistically significant differences regarding fetal parameters and peak amplitudes of the oxytocin stimulated pregnant rat myometrial strips among groups. In L-NAME group at 0 and 0.1 mIU/ml oxytocin, the contraction frequency in a ten-min period was statistically lower than the control group (Z = -2.850, p = 0.004; Z = -2.902, p = 0.004, respectively). In MgSO4 group only at 0 mIU/ml oxytocin, the frequencies of the contractions in ten-min period were statistically lower than the control group (Z = -2.973,p = 0.003). In L-NAME + MgSO4 group at 0, 0.1 and 0.2 mIU/ml oxytocin concentrations the frequencies of the contractions in ten-min period were statistically lower than the control group (Z = - 4.018, p = 0.000; Z = -3.237, p = 0.001; Z = -2.902, p = 0.004, respectively). In L-NAME + MgSO4 given group at each oxytocin concentrations, the frequencies of the contractions in ten-min period were lower but not statistically different than the L-NAME group. CONCLUSION: MgSO4 has no significant effect on the amplitude of spontaneous or oxytocin induced myometrial contractions, but decreased the frequency of spontaneous contractions. At each doses of oxytocin, MgSO4 has no significant effect on the frequency of contraction in a pregnant rat model of preeclampsia induced by L-NAME.

Efficacy of in-feed preparations of an anticoccidial, multienzyme, prebiotic, probiotic, and herbal essential oil mixture in healthy and Eimeria spp.-infected broilers.

The efficacies of 5 widely used dietary supplements were investigated on performance indices, fecal oocyst excretion, lesion score, and intestinal tract measurements in healthy and Eimeria spp.-infected birds by using a comparative model. This study included 2,400 sexed Ross 308 broiler chicks that were equally divided in 2 groups: the infected group, experimentally infected with oocysts of mixed Eimeria spp. at 14 d of age, and the healthy controls. The birds in both groups were further divided equally into 6 groups, of which one was fed a basal diet and served as control without treatment and the other 5 served as experimental treatments. These 5 groups were fed 5 diets containing preparations of 60 mg/kg of anticoccidial salinomycin (SAL), 1 g/kg of multienzyme (ENZ), 1 g/kg of probiotic (PRO), 1 g/kg of prebiotic (PRE), and 40 mg/kg of an herbal essential oil mixture (EOM). Body weight gain and feed conversion ratio (FCR) showed significant improvement in the infected animals, which indicates that dietary supplemental regimens with SAL, ENZ, PRO, and PRE initiated in 1-d-old chicks reduced adverse effects after challenge with coccidiosis; however, chicks that were administered EOM failed to show such improvement. Uninfected chickens showed significant improvement in FCR with supplements SAL, PRE, and EOM, which signifies significant (P < 0.01) infection by supplement interactions for BW gain and FCR. In the infected group, all of the supplements reduced the severity of coccidiosis lesions (P < 0.01) induced by mixed Eimeria spp. through the middle and lower regions of the small intestines, whereas supplementation with SAL or EOM alone was effective (P < 0.01) in reducing oocyst excretion compared with the control treatment. The data indicated that use of these subtherapeutically efficacious supplements (except EOM) in broiler production can lessen the depression in growth due to coccidial challenge.

MicroRNA-regulated molecular mechanism underlying bovine subclinical endometritis.

An impaired uterine environment triggered by the incidence of subclinical endometritis often compromises fertility in the bovine. The uterus is a dynamic organ with tight regulation of specific genes at the transcriptional and translational levels. Herein, we hypothesised that subclinical endometritis alters the expression of uterine microRNAs (miRNAs), which may result in the dysregulation of corresponding target genes and biological pathways. To test this hypothesis, we used a genome-wide RT(2) (Exiqon, Vedbaek, Denmark) miRNA PCR array consisting of 354 miRNA primers and analysed miRNA expression in uterine cytobrush samples taken from cows with and without subclinical endometritis. The results revealed aberrant expression of 23 miRNAs in cows with subclinical endometritis compared with healthy cows. Furthermore, we designed an in vitro endometrial cell culture model challenged by lipopolysaccharide (LPS) to validate the differential regulation of miRNAs in cytobrush samples. Interestingly, we observed similar expression miRNA patterns in cytobrush samples taken from cows with or without subclinical endometritis and in vitro cultured endometrial cells challenged by LPS. To trace signalling pathways and biological functions potentially controlled by the aberrantly expressed miRNAs, we filtered high-ranking target genes from miRBase and analysed them using ingenuity pathway analysis. The gene networks, canonical pathways and biological functions strikingly converged to signalling pathways that mediate inflammatory responses, cellular proliferation, cell movement, the cell cycle and apoptosis in the bovine endometrium. In addition, expression analysis of key genes from the gene networks confirmed their presence and the potential regulation of these genes by uterine miRNAs. Furthermore, luciferase assay data substantiated the primary information from bioinformatic prediction that generated potential target genes for the dysregulated miRNAs in subclinical endometritis. Together, these data suggest the potential regulatory role of uterine miRNAs in the development and progression of bovine subclinical endometritis.

The spectroscopic (FT-IR, FT-Raman, UV and NMR) first order hyperpolarizability and HOMO-LUMO analysis of dansyl chloride.

The solid phase FT-IR and FT-Raman spectra of dansyl chloride (DC) have been recorded in the regions 400-4000 and 50-4000 cm(-1), respectively. The spectra have been interpreted in terms of fundamentals modes, combination and overtone bands. The structure of the molecule has been optimized and the structural characteristics have been determined by density functional theory (B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies were calculated for most stable conformer and were compared with the experimental frequencies, which yield good agreement between observed and calculated frequencies. The infrared and Raman spectra have also been predicted from the calculated intensities. (1)H and (13)CNMR spectra were recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. UV-Visible spectrum of the compound was recorded in the region 200-600 nm and the electronic properties HOMO and LUMO energies were measured by time-dependent TD-DFT approach. Nonlinear optical and thermodynamic properties were interpreted. All the calculated results were compared with the available experimental data of the title molecule.

Identification of structural and spectral features of synthesized cyano-stilbene dye derivatives: a comparative experimental and DFT study.

The synthesized three dye derivatives of cyano-stilbene monomer were identified by experimental spectroscopic techniques and density functional approach. The optimized geometrical structure, vibrational and electronic transitions along with the nonlinear optical (NLO) properties of those compounds were presented in this study. The vibrational spectra of investigated compounds were recorded in solid state with FT-IR and FT-Raman spectrometry in the range of 4000-400 cm(-1) and 3600-50 cm(-1), respectively. The theoretical ground state equilibrium conformations and vibrational wavenumbers were carried out by using density functional method with 6-311G(d,p) basis set. Assignments of the fundamental vibrational modes were examined on the basis of the measured data and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The UV absorption spectra of monomers were observed in the range of 200-600 nm in chloroform, acetonitrile and toluene, and time dependent DFT method was used to obtain the electronic properties. The linear polarizability and first hyperpolarizability of the studied molecules indicates that the title compounds can be used as a good nonlinear optical material. A detailed description of spectroscopic behaviors of compounds was given based on the comparison of experimental measurements and theoretical computations.